作者单位：529031 江门，广东省江门市中心医院 中山大学附属江门医院肿瘤科(谭洁媚，李明毅)；510000 广州，中山大学肿瘤防治中心内科(梁颖)

miRNA-132通过靶向调控Bmi-1表达影响鼻咽癌细胞对放射治疗敏感性

谭洁媚李明毅梁颖

【摘要】目的研究miRNA-132对鼻咽癌细胞放射治疗敏感性的影响。方法使用miRNA芯片技术，对比5-8F(亲代细胞)和5-8F/R(放射治疗抵抗细胞)中miRNA表达水平差异，从中挑选差异最为明显的miRNA-132作后续研究。使用流式细胞仪检测miRNA-132对细胞凋亡的影响。使用双荧光报告素酶、蛋白免疫印迹法等方式验证miRNA-132的下游靶基因。结果miRNA-132可以促进鼻咽癌5-8F/R细胞的凋亡，提高其对放射治疗的敏感性，还可以抑制其体内的生长能力。miRNA-132可以抑制Bmi-1信使RNA和蛋白质表达水平。结论miRNA-132可通过抑制下游靶基因Bmi-1来发挥其放射治疗增敏功能。

【关键词】miRNA-132；Bmi-1；鼻咽癌；放射治疗增敏

DOI:10.3969/g.issn.0253-9802.2015.07.003

Abstract【】ObjectiveTo investigate the effect of miRNA-132 on the sensitivity of nasopharyngeal carcinoma (NPC) cells to radiotherapy. MethodsThe expression levels of miRNAs were compared between 5-8F parental cells and 5-8F/R radioresistant cells using a miRNA array; miRNA-132, which showed the most prominent changes between the two cell lines, was chosen for further study. The effect of miRNA-132 on apoptosis was examined using flow cytometry. A dual-luciferase reporter assay and western blotting were employed for the identification and verification of the downstream targets of miRNA-132. ResultsmiRNA-132 promoted apoptosis, enhanced radiosensitivity in 5-8F/R cells and inhibited the in vivo growth of 5-8F/R cells. In addition, miRNA-132 suppressed Bmi-1 expression at both the mRNA and protein levels. ConclusionmiRNA-132 enhanced the radiosensitivity of NPC cells via negative regulation of its downstream target Bmi-1.

收稿日期：(2015-01-06)

miRNA-132 affects the sensitivity of nasopharyngeal carcinoma cells to radiotherapy via targeted regulation of Bmi-1 expressionTanJiemei，LiMingyi,LiangYing.DepartmentofOncology,JiangmenHospitalofSunYat-senUniversity,Jiangmen529031,China

【Key words】miRNA-132；Bmi-1；Nasopharyngeal carcinoma；Radiosensitization

鼻咽癌是中国南方最主要的恶性肿瘤之一。目前，放射治疗是鼻咽癌公认的治疗首选方式，但约55%的鼻咽癌在放射治疗后5年内出现复发转移，导致治疗失败[1-2]。导致鼻咽癌对放射治疗产生抵抗的原因很多，主要有癌基因的异常表达，肿瘤微环境的异质性，相关信号通路的异常等[3-5]。近年来，越来越多的证据表明，miRNA不仅参与了正常组织的分化、发育，还参与了肿瘤的发生和进展。同时，miRNA的异常表达还与肿瘤细胞对放射治疗、化学治疗产生抵抗密切相关[6-7]。有文献表明，miRNA的异常表达常导致鼻咽癌对放射治疗产生抵抗，这也是鼻咽癌患者复发的重要原因[8-10]。……